Background. The study of bone marrow involvement is a necessary step in disease staging, both in non-Hodgkin lymphomas and in the case of Hodgkin lymphoma (HL). The standard assessment of bone marrow lesion is carried out based on immunohistochemical examination of bone marrow trepanobioptate, and recently computer technologies (positron emission tomography combined with computed tomography) have been introduced to assess bone marrow involvement. At the same time, immunological methods for detecting tumor cells using multicolor flow cytometry are more available. In addition, they allow for detailed study of the tumor bone marrow microenvironment.Aim. To evaluate the immunomorphological features of bone marrow in HL and the possibility of identifying specific bone marrow lesions using flow cytometry.Materials and methods. The study included the analysis of 107 bone marrow samples. The samples were obtained from 107 patients with various variants of classical HL, diagnosed and treated at the Lapino Clinical Hospital and the P.A. Herzen Moscow State Medical Institute from 2018 to 2022.Results. The features of bone marrow lymphocytes subpopulation in patients with classical HL are shown.Conclusion. An immunological assessment of bone marrow involvement degree was carried out, data from flow cytometry and immunohistochemical examination of trephine biopsy specimens during primary diagnosis were compared, and the features of bone marrow lymphocytes subpopulation were evaluated. The interrelation of these factors at the diagnostic stage in classical variants of HL was studied. At the end of treatment, the primary immunological data (the degree of bone marrow involvement) were compared with the results of the positron emission tomography combined with computed tomography.

Proton therapy presents an appealing radiotherapy modality for the treatment of deeply-seated and unresectable tumors, but it still needs additional means to enhance the localization and efficiency of therapeutic action. Here we explore the use of elemental bismuth nanoparticles (Bi NPs) as sensitizers for proton therapy enhancement. Spherical Bi NPs were prepared by the method of pulsed laser ablation, followed by their coating with Pluronic polymer to stabilize them in a physiological environment. We observed efficient apoptotic cell death after proton irradiation at the Bragg peak, which was explained by high proton stopping power and low work function of Bi. The maximal effect was observed for 3 Gy radiation and 50 mu g/mL NPs dose with 97 % inhibition of tumor cell clonogenic activity. The strong therapeutic effect was confirmed in vivo using aggressive Sa37 sarcoma tumors in mice. We observed 60 % inhibition of primary tumor growth with a decrease of metastatic potential in popliteal and axillary lymph nodes. Combined with X-ray contrast properties and radiosensitizing functionalities, the proposed concept of Bi NPs-enhanced proton therapy promises a major upgrade for cancer therapy.

The paper presents a clinical case related to the implementation of a surgical step-by-step method of treating a patient with malignant rectal formation, progression of the underlying disease, against the background of a paravesical abscess in the pelvis, after previously comprehensive treatment. The tactics of therapeutic measures consisted, at the first stage, in the rehabilitation of the pelvis, the resolution of a paravesical abscess, followed by simultaneous excision of the soft tissues of the perineum, resection of the ileum, the formation of enteroenteroanastomosis, the formation of a heterotopic urinary reservoir according to Bricker, plasty of the defect of the perineum with a VRAM flap. An important condition for the implementation of the treatment plan is to conduct an interdisciplinary consultation with the involvement of specialists of various profiles, which is aimed at resolving the oncological process and complications of its treatment.

The paper presents information on results of spiral computed tomography of patients with lung cancer. The radiological examination was carried out at the out-patient Department of A. Tsyb MRRC in Obninsk. In addition to lung tumor, changes in pulmonary tissue of various origin were also observed. Diagnostic examinations of patients with lung cancer of II and III stages were performed in the polyclinic of A. Tsyb MRRC in accordance with the regulated clinical terms. The results obtained give grounds for correction of lung pathology, which is necessary for the subsequent chemoradiation therapy of the tumor in the required volume. From the analysis of the accumulated examination protocols it can be concluded that the timely detection and treatment of inflammatory changes in the pulmonary tissue is effective and necessary in the treatment of lung cancer and improves the quality of patients life.

Comparative data on the irradiation of patients with cancer with beams of carbon ions using passive field-modification methods and an active method of dose formation are presented based on publications and our own data. Assessments are given on the physical and radiobiological features of the formation of active and passive fields, the immediate results of treatment, and doses outside the irradiation field for both methods are considered.

Objective: to identify the characteristic echographic features of benign ovarian tumors using the recommendations of the IOTA group.Materials and methods. Five articles published in the journal Ultrasound in Obstetrics & Gynecology for 2008–2019 were analyzed. Each article is devoted to a histologically verified pathology of the ovaries, representing four morphological variants of an ovarian tumor (strum, fibroma/fibrothecoma, uroepithelial tumor (Brenner's tumor) and cystadenofibroma, as well as endometrioma in pregnancy. The total number was 380 women. When describing pathological formations, the researchers used a single protocol recommended by the IOTA group. Evaluated twentyone parameters, including the morphology of the formation, the structure of fluid inclusions and the solid component, the presence of fluid in the retrouterine space and ascites, as well as the degree of tumor vascularization.Results. The analysis of the struma, fibroma (fibrothecoma), Brenner tumor, cystadenofibroma and endometrioma of pregnant women indicates that there are no reliable criteria for diagnosing the histological structure of the tumor, both by the age of the patients, the size of the formation, and by ultrasound signs. Hyperechoic inclusions, which are noted only in Brenner tumors, both benign and malignant, can serve as the only marker among the pathology under consideration. In the study of the listed benign neoplasms of the ovaries, no features of the blood supply were revealed. All neoplasms had vascularization from the complete absence of vessels (1 point) to their moderate number (3 points). Hypervascularization (4 points) occurred in struma, fibroma (fibrotecoma), and cystadenofibroma.Conclusions. The task of ultrasound examination is the timely detection of an ovarian tumor with a presumptive conclusion of the probability of malignancy, based on standardized protocols of the IOTA group, which is important for the correct routing of the patient.

The biological effects of proton irradiation with high and ultrahigh dose rates (up to 0.3 MGy/s) of cultured human tumor and normal cells at the Bragg peak and beyond the peak were studied. Flow cytometry was used to study the level of apoptosis and some other characteristics of cells. It was found that in the mode of single-pulse irradiation in the Bragg peak, the level of apoptosis of tumor cells significantly increased.

Today, photodynamic therapy (PDT) is one of the most promising methods for the complete eradication of a number of superficial solid malignant neoplasms. In this work, we studied the ef-fectiveness of PDT on Ehrlich carcinoma of mice with the injections of a new photosensitizer (PS) Photoran E6. To determine the optimal drug-light interval, from the time of PS injection to laser ir-radiation, we studied the distribution kinetics of Photoran E6 in tumors and healthy tissues sur-rounding them. In assessing the response of the inhibitory effect of Ehrlich carcinoma to PDT, the following indicators were used: inhibition of tumor growth (ITG, %), complete regression (CR, %), absolute growth rates of tumors (K) in mice with continued growth of neoplasia, and an increase in life expectancy (ILE, %) of individuals in the experimental groups compared with the control, according to the criterion of curing animals: the absence of signs of tumor recurrence within 90 days after therapy. The therapeutic potential of PDT for tumor cell devitalization was determined by histological examination of the areas of exposure to laser radiation at 21d after treatment. The results showed that Photoran E6 has a high antitumor activity for PDT of solid Ehrlich carcinoma. Conducting PDT in the optimal time after the injection of PS with certain parameters of laser ex-posure allows to achieve the maximum inhibitory effect on malignant neoplasms. A pathomor-phological study in the areas of photodynamic exposure of the surviving tumor cells was not found.

Purpose: analysis of echographic signs of benign and malignant formations of the uterine appendages using the recommendations of the IOTA group.Materials and methods. 17 articles published in the journal Ultrasound in Obstetrics & Gynecology for 2007–2020 were analyzed. Each article is devoted to the histologically verified pathology of the uterine appendages, of which 431 are benign and 1205 are malignant neoplasms. When describing pathological formations, the re-searchers used a single protocol recommended by the IOTA group. 21 parameters were assessed, including the morphology of the formation, the structure of fluid inclusions and solid component, the presence of fluid in the posterior uterine pocket and ascites, as well as the degree of tumor vascularization.Results. Аll ultrasound signs of tumors were found in both groups, but the frequency of their occurrence was different. Thus, unilocular neoplasms were more often detected in benign tumors than in malignant ones (p = 0.05). Also, acoustic shadows were found significantly more frequently in benign tumors (p < 0.05). When assessing tumor morphology, attention should be paid to tendencies that are more characteristic of malignant tumors, which include a solid structure (p = 0.13) and the occurrence of ascites (p = 0.13), while a multilocular structure without a solid component was more common in benign (p = 0.10). The size of the neoplasm, uneven contour, papillary growths, hyperechoic inclusions and the nature of the internal contents of the cystic cavities are found with approximately the same frequency in both groups. When as-sessing the blood supply to a pathological formation, hypervascularization confidently indicated a malignant tumor (p < 0.05), while avascularization in such neoplasms was rare, however, the differences with benign ones were insignificant (p = 0.06).Conclusions. There are no reliable echographic signs of the nature of the neo-plasm. The set of criteria will improve the quality of preoperative ultrasound diagnostics of ovarian tumors.

Purpose: The paper deals with the occurrence of prostate cancer and mean survival time following a diagnosis of the disease among Chernobyl clean-up workers. Material and methods: Clinical and dosimetry data accumulated at the National Radiation and Epidemiological Registry (NRER) during the period from 1996 over 2018 were used for the study. The study cohort consisted of 69,698 men. During the follow-up 742 prostate cancer cases were detected, all patients had radiation dose records, the disease stage was established in 628 patients. To assess radiation risk maximum likelihood approach was used. Mean survival time was evaluated with the use of the relationship between a disease prevalence and newly detected disease cases intensity in a stationary population (diseases intensity is equal to intensity of mortality from all causes). Results: Excess relative risk of prostate cancer induction per 1 Gy was 0.74 (95 % CI: ‒0.31; 2.15) and it was statistically insignificant. Standardized incidence ratios between clean-up workers and male population of Russia within 95 % confidence limits do not differ from 1.0. Mean survival time after the disease diagnosis within the period from 1996 over 2018 was 3.5±1.3 years. The relationship between a survival time and a disease stage was estimated. Survival time for cases with 1–3 stages 3.3±2.9, 3.6±2.3, 4.3±2.7 years respectively. The less survival time for cases with stage 4 was 1.5±0.8 years. Mean mortality rate, i.e. the ratio of the number of clean-up workers died from prostate cancer to the total number of clean-up workers with diagnosed prostate cancer was 36.8 %, for stages 1–4 it was 20, 16, 37, 74 % respectively. Mean survival time in the groups with doses less than and higher than 150 mGy was 3.4±1.4 and 3.7±1.7, respectively. Presented data confirm the null hypothesis that there is no difference in survival times (p=0.20). Conclusion: Increase in prostate cancer incidence becomes the social problem not only in Russia but in other countries as well. The paper presents results of comprehensive radiation epidemiological analysis of prostate cancer incidence in cleanup workers, who constitute the representative sample of the Russian male population. The dose ‒ prostate cancer incidence relationship for the follow-up period from 1996 over 2018 is not statistically significant, although the value of excess relative risk per dose unit is positive. It is not unthinkable that the absence of statistical significance is caused due to limited length of the follow-up period. But at the same time, the fact that observed the standardized incidence ratio is 1.0 and characteristics of two groups with doses ≥150 mGy are similar, speaks of the lack of a significant radiation effect. The obtained results of the analysis confirm our view of the necessity to continue the study.

Photodynamic therapy (PDT) is a local form of treatment for the complete eradication of solid malignant neoplasms (PDT). In this work, we studied the efficiency of PDT with the photosensi-tizer (PS) chlorin e6 dimethyl ether (DME Che6) in the treatment of positive for the mutant p53 gene sarcoma M-1. To assess the optimal time for tumor irradiation with laser the kinetics of PS accumulation in tumor and surrounding healthy tissues was studied. The tumor response to PDT was assessed with the use of the following criteria: tumor growth inhibition index (%); tumor complete regression (%); absolute growth rate (K) index, it is used in rats with tumor growth after the treatment; increase in the life expectancy in group of treated animals and the control group of tumor-bearing rats; the treatment response criterion – means the absence of signs of tumor re-currence within 90 days after therapy. On the 21st day after the treatment the PDT efficiency for tumor cells devitalization was assessed by examining the areas exposed to laser radiation and data of histological analysis. Results of the study allow us to state that DME Che6 has a high anti-tumor activity in the treatment of M-1 sarcoma. The maximum inhibitory effect of the PS on ma-lignant neoplasms after PDT is achieved if time between the sensitizer introduction and the laser irradiation beginning is optimal. As a result of pathomorphological assessment of material after PDT, no survived tumor cells with expression of the mutant p53 protein were detected.

Background. Application of mathematical modeling for search for biologically active molecules is currently a promising scientific approach. Application of numerical algorithms for optimization of peptide sequences and molecular dynamics allowed to obtain modified peptide sequences that are functional analogs of the sequence of natural inhibitor of cyclin-dependent kinase 4/6 p16INK4a.The study objective is to establish biological characteristics of peptide sequences of CDK 4/6 inhibitors obtained using mathematical modeling.Materials and methods. The studies were performed in vitro using tumor cell lines (MCF-7, А549, SKOV-3, НСТ116). Apoptosis level, cell distribution per cell cycle stages, changes in Bcl-2 expression, changes in the level of phosphorylated pRb under the effect of the studied molecules were investigated using flow cytometry. Proliferation dynamics of cell populations were studied using RTCA iCELLIgence biosensor technology.Results. Peptide sequences obtained using mathematical modeling decrease the level of phosphorylated pRb, Bcl-2 expression when applied to actively proliferating cells. These proteins serve as molecular targets for the cyclin-dependent kinase 4/6–cyclin D complex, and changes in pRb and Bcl-2 levels might indicate inhibition of complex formation. Consequently, decreased proliferative activity and increased apoptosis were observed. Effectiveness of the peptide sequences depended on their molecular structure and type of the used cell line. Two (2) of the studied modified peptide sequences have higher antiproliferative and proapoptotic effect on tumor cells than native p16INK4a (90-97) sequence.Conclusion. Application of mathematical modeling for search and development of functionally active molecules allowed to create peptide sequences with stronger cyclin-dependent kinase inhibitor effect than p16INK4a, the native inhibitor CDK4/6.

Фотодинамическая терапия карциномы Эрлиха мышей с липосомальным борированным хлорином е6Абрамова О.Б., Дрожжина В.В., Чурикова Т